Surgical regenerative therapy for peri-implantitis—a comprehensive review and what is the current histological evidence?

Lasers are increasingly being applied as a monotherapy or adjunct to surgical and nonsurgical therapy in the treatment of periodontitis and peri-implantitis. Numerous clinical studies evaluating the effectiveness of lasers in periodontal therapy as well as critical and systematic reviews of this research have been reported in the literature. The therapeutic goals of using lasers, or specific laser wavelengths, as a monotherapy or adjunct to traditional therapies, include root surface debridement and detoxification, reduction in specific or overall subgingival bacterial composition, subgingival curettage, suppression of inflammation, biostimulation, and periodontal regeneration. Low-level lasers have been used in conjunction with photosensitizers, such as toluidine blue, which adhere to the bacterial membrane, to induce a photochemical cytotoxic reaction intended to eradicate periodontopathic bacteria (i.e., antimicrobial photodynamic therapy). The conclusions of current systematic reviews are inconsistent, reflecting, in part, inconsistencies in clinical protocols, therapeutic and biological endpoints, procedural heterogeneity, and inadequate description of interventions. Nevertheless, systematic reviews conclude that clinical outcomes of laser treatment are similar or slightly better than reference nonsurgical or surgical therapies; however, any differential benefits remain short term. Moreover, there is limited human histologic evidence that is consistent with the potential for periodontal regeneration following laser-assisted therapy in patients with moderate to severe periodontitis. To capitalize on cellular and molecular changes incurred by laser interactions with hard and soft tissues of the periodontium and peri-implant tissues, laser treatment protocols should be refined to optimize lasers as a tool in our dental armamentarium. There is much promise for improved treatment outcomes with inclusion of dental lasers in the treatment of periodontal and peri-implant disease.

Introduction:One of the most important goals of periodontitis therapy is the elimination of deep periodontal pockets. In regenerative periodontal therapy, different types of bone grafts, membranes, growth factors, etc. are used to improve regeneration of lost periodontal tissue.The aim of this study was to evaluate the effect of surgical therapy supported by the use of bone replacement material in the treatment of deep intrabony pockets, compared to surgical treatment (flap surgery) without the use of bone replacement in advanced periodontitis.Methods and materials:The study included 50 patients of both sexes with advanced periodontitis, divided into two groups. After initial periodontal therapy was performed, plaque index (PI), papillary bleeding index (PBI) were verified, and depth of periodontal pockets was measured in both groups. One group (group 1) of the patients underwent surgical therapy, open flap surgery, while the other group (group 2) underwent the same surgical treatment method (open flap surgery), during which bone defects were filled with bone replacement material.Results:The results showed that both group 1 and group 2 experienced improvements after periodontal surgical therapy. In group 1, there are no statistically significant changes in all three plaque index measurements (PI), while there has been a significant reduction in PI in group 2 following the surgery. For the PBI index, it was determined that there were statistically significant changes in values in group 1, both after surgical procedures and six months later, as well as in group 2. Statistical analysis of the results of the probing depth of pockets has shown that there are significant changes in the measurement of the depth of periodontal pocket one month after the surgery, as well as six months later, meaning that there has been a significant reduction in the depth of the periodontal pocket one month following the surgery as well as six months later, for both groups. However, we did not determine a statistically significant difference in the probing depth of pockets between these two groups.Conclusion:Six months after a surgical therapy, clinical parameters showed a reduction of the probing depth of the periodontal pocket in both examined groups. The use of bone replacement did not yield significantly better results in reducing the depth of probing compared to the standard flap surgery. We believe that future research should focus on testing the effectiveness of new regenerative methods and materials (bone replacements with various properties, membranes, and surgical methods) that will result in better treatment results with predictable outcomes.

Focused Clinical Question: How should periodontal furcation defects be managed via periodontal regenerative therapy, and what parameters should be used for treatment selection? Summary: The treatment of furcation defects can vary based on the type and location of the furcation involvement. Attaining predictable regenerative outcomes is dependent on the control of local and systemic factors. A combined treatment approach (barrier and bone replacement graft with or without biologic) generally offers the better therapeutic outcome over monotherapy. Class I furcation defects can be managed via conventional periodontal non-surgical and/or surgical therapy, whereas Class II furcation defects generally attain better outcomes with regenerative therapy. There is weak evidence, limited to case reports, that Class III furcation defects can be treated successfully with regenerative therapy. Conclusions: In Class I furcation defects, regenerative therapy might be beneficial in certain clinical scenarios, although most Class I furcation defects can be treated successfully with non-regenerative therapy. For successful treatment of maxillary and mandibular molars with Class II furcation defects, systemic and local factors should be controlled, and surgical debridement and postoperative maintenance should be performed adequately. Although there is limited evidence for regeneration of Class III furcation defects, there may be a modest improvement allowing for tooth retention. Ultimately, the benefit of tooth retention and cost should be considered in the indication of therapy for teeth with severe furcation involvement.

This study aimed to investigate retrospectively the outcome of surgical periodontal therapy. Periodontal surgeries implemented at General Dentistry, Tokyo Dental College Suidobashi Hospital during the period of April 2010 through March 2012 were subjected to data analysis. After initial periodontal therapy, 17 clinicians performed a total of 138 periodontal surgeries in 80 patients with moderate to advanced periodontitis (31 men and 49 women; mean age 54). Cases (sites) operated were as follows: open flap debridement=102, periodontal regenerative therapy=29 (17 for intrabony defects, 12 for furcation involvements) and periodontal plastic surgery=7. Enamel matrix derivative or bone graft was used for regenerative therapy. Clinical data were analyzed focusing on the comparison between open flap debridement and regenerative therapy. At 5 months after open flap debridement, mean reduction in probing depth (PD) and gain in clinical attachment level (CAL) was 3.9 mm (range -1.0-9.0) and 2.3 mm (range -1.0-9.0), respectively. The corresponding values with regenerative therapy were 4.0 mm (range 0-8.0) and 2.8 mm (-1.0-6.0), respectively. At sites with initial PD≥8 mm, a significantly greater gain in CAL was obtained with the regenerative therapy than with flap surgery (mean CAL gain 4.3 mm vs. 2.9 mm, p<0.05). Periodontal surgery performed in our clinical setting demonstrated a favorable short-term outcome. Our data suggest the efficacy of regenerative therapy, in particular for the treatment of deep pockets.

The serendipitous discovery of osseointegration and the subsequent development of dental implants have irrefutably marked an epoch-making point of inflection in not only the basic approach of the clinicians toward treating edentulism but also in the attitudes and preferences of the patients in getting their oral rehabilitation issues resolved. This decisive shift also triggered explosive research targeting improvement in various aspects of dental implants. However, initial success in osseointegration does not necessarily translate into success in long-term function. A successfully osseointegrated implant may be afflicted with early or late complications in due course of service. Of these, peri-implantitis (PI) is considered one of the most common causes of implant failure. For the treatment of peri-implant diseases (mucositis and PI), various conservative and surgical approaches are available. Mucositis and moderate forms of PI can be contained effectively using conservative methods. These include the administration of systemic and local antibiotics alone or in conjunction with other treatment modalities such as nonsurgical therapy which consists of mechanical debridement of the affected areas, irrigation with antiseptics (such as chlorhexidine, saline, and 10% hydrogen peroxide) with or without surface decontamination, laser-supported therapy, photodynamic therapy as well as light-activated disinfection also known as photodynamic antimicrobial chemotherapy along with maintaining adequate plaque control. In cases with advanced PI, surgical therapies are more effective than conservative approaches. Open flap debridement can be done, and depending on the configuration of the defect, regenerative therapies such as guided tissue regenerative and the use of bone graft materials may be applicable for defect filling whereas resective surgery can be considered for the elimination of peri-implant lesions.

Peri-implantitis is an increasingly prevalent condition that, if left untreated, can lead to implant failure and loss. Numerous regenerative treatment modalities have been reported in the literature with varying degrees of success. Unfortunately, there is little consensus regarding optimal methods for predictable regeneration of the peri-implant bone lost due to the disease. This case report presents a 68-year-old healthy, nonsmoking man with peri-implantitis affecting the endosseous implant that replaced the maxillary left first molar. After unsuccessful nonsurgical debridement, regenerative surgical therapy was recommended. Guided bone regeneration (GBR) was performed using natural bovine bone mineral covered with a dehydrated human deepithelialized human amnion-chorion membrane (ddACM). Implant surface decontamination was achieved using a titanium brush. Posttreatment clinical assessment suggested that the patient responded well to surgical regenerative therapy. This response was characterized by the reestablishment of healthy peri-implant soft tissues. From a radiographic perspective, complete bone fill of the peri-implant bony defect was seen. These outcomes were maintained over 2 years. This case demonstrates that it is possible to treat peri-implantitis successfully and obtain stable long-term results with a GBR approach utilizing a xenogeneic bone substitute with ddACM.

Factors influencing the outcome of regenerative therapy of Class II furcations are incompletely and poorly understood. The purpose of this 24-month prospective study was to examine the relationship of patient-, site-, and treatment-related factors to the clinical closure of randomly selected mandibular Class II furcations. Results of therapy were evaluated at 1 and 2 years postoperatively. One-year outcome data are presented in this report. A total of 43 otherwise healthy individuals with chronic periodontitis (26 male, 17 female), 36 to 70 years of age, completed the 12-month evaluation of the study. Entry criteria included clinical and radiographic evidence of two or more mandibular facial Class II furcation defects (> or = 3 mm horizontal probing depth). Surgical therapy was completed by four periodontists (two each) in either a university clinic or private practice. Each patient contributed two furcation defects that were treated by combination therapy using an expanded polytetrafluoroethylene (ePTFE) membrane and demineralized freeze-dried bone allograft (DFDBA). Clinical measurements included a gingival index, plaque index, mobility, and, referencing an occlusal stent, probing depth (PD), probing attachment level-vertical (PAL-V), and probing attachment level-horizontal (PAL-H). Multiple linear measurements were recorded for each site clinically and after surgical debridement to characterize defect morphology, root configuration, and barrier placement. Defect volume was computed mathematically. Postsurgical maintenance care was provided at 1 to 2, 4, 6, and 8 weeks, and then biweekly until 3 months, with subsequent supportive periodontal maintenance visits at 3-month intervals. The clinical status of the furcation (open or closed), measured by a non-treating periodontist at 1 and 2 years, was the primary outcome measure. The association of patient-related factors (e.g., smoking), site-related factors (e.g., root configuration and defect morphology), and treatment-related factors (e.g., membrane exposure) to clinical status of furcations was assessed using random effects hierarchical logistic regression analysis, controlling for design and demographic variables. Non-parametric analysis was used for specific group comparisons. Complete clinical closure was achieved in 74% of all sites. Of the residual furcation defects, 68% were reduced to Class I. No defects progressed to Class III. Significant improvements in mean PD and PAL-V were obtained following surgical therapy. Although the proportion of sites demonstrating complete furcation closure was comparable for smokers and non-smokers, the proportion of Class II residual defects was significantly higher among smokers than non-smokers (62.5% versus 14.3%, respectively). Increases in presurgical PAL-H were associated with monotonic decreases in the percentage of sites demonstrating complete clinical closure, with only 53% of lesions > or = 5 mm responding with complete closure. Similarly, significant reductions in the frequency of clinical closure were associated with increases in the distance between the roof of furcation and crest of bone, roof of furcation and base of defect, depth of horizontal defect, and divergence of roots at the crest of bone. The successful clinical closure of Class II furcations was achievable at 1 year following combination therapy with an ePTFE membrane and DFDBA. The highest frequency of clinical furcation closure was observed in early Class II defects. Furcations with vertical or horizontal bone loss of 5 mm or greater responded with the lowest frequency of complete clinical closure. Nevertheless, complete furcation closure was achievable in 50% of molars with extensive bone loss. Also, 15 out of 22 (68%) of all residual defects were reduced to Class I and only seven (8%) failed to improve, demonstrating that successful clinical resolution of advanced defects remains an attainable goal.

Although hyaluronic acid (HA) has long been used for many medical applications, only in recent years has it gained greater popularity in the field of periodontics because of its biological effects during wound healing. Even today, most clinicians are not aware that more than one type of HA exists and that the extent of its biological functions may vary depending upon the particular characteristics of the biomolecule itself. To review and synthesize the current preclinical and clinical evidence on the biological effects and therapeutic applications of HA in periodontology, with a focus on its role in wound healing and regeneration. The origin and chemical structure of HA are discussed first, with a focus on the importance of its molecular weight and the possibility of modifying its structure and form. The main biological properties of HA followed by its effects on the cells of periodontal tissues are summarized and followed by the presentation of the results from preclinical studies in animals which have evaluated the effects of HA in various types of defects. Subsequently, the data from clinical studies evaluating the application of HA in nonsurgical periodontal therapy, regenerative periodontal surgery, and mucogingival surgery are summarized, and recommendations for the clinicians are provided. The preclinical and clinical evidence indicates that HA accelerates the wound healing process through inflammatory mechanisms and enhances blood clot stability when applied to the root surface. It also influences the expression of both mineralized tissue markers and cementoblast-specific genes, suggesting a potential role in cementum regeneration. HA strongly promotes osteoprogenitor growth while maintaining stemness, potentially regulating the balance between self-renewal and differentiation during bone regeneration. Additionally, HA enhances periodontal ligament (PDL) cell adhesion and proliferation. It has been shown to improve the proliferative and migratory abilities of cells while inducing the expression of collagen type III alpha 1 (COL3A1) and TGFβ-3 genes, which are characteristic of scarless fetal wound healing. Certain HA formulations upregulate the expression of genes encoding platelet-derived growth factor B (PDGFB), fibroblast growth factor 2 (FGF-2), and epidermal growth factor (EGF), all of which play crucial roles in the healing process. Histologic evidence from animal studies suggests that HA may promote periodontal regeneration when applied both non-surgically and surgically-particularly in intrabony defects, gingival recessions, and, to some extent, in furcation defects. The data from clinical studies revealed that HA leads to statistically significant and clinically relevant improvements of probing depths and clinical attachment levels when used in conjunction with nonsurgical periodontal therapy and surgical therapy in intrabony and recession defects. The available data from preclinical and clinical studies provide robust evidence on the effects of HA to enhance periodontal wound healing and regeneration, and on the improved clinical outcomes when HA is used in conjunction with nonsurgical periodontal therapy and regenerative surgery in intrabony and recession defects.

Analysis of the 3-dimensional implant position, the bone defect morphology, and the soft tissue situation guides the decision to preserve or to remove an implant with a severe peri-implantitis lesion. The aim of this narrative review was to analyze and to comprehensively illustrate the treatment options focusing on peri-implant bone regeneration in presence of severe peri-implant bone loss. A database search was performed independently by the two reviewers to identify case reports, case series, cohort, retrospective, and prospective studies about peri-implant bone regeneration with a follow-up of at least 6 months. Of the 344 studies issued during the database analysis, 96 publications were selected by the authors for this review. Deproteinized bovine bone mineral remains the best documented material for defect regeneration in peri-implantitis in combination with or without a barrier membrane. While studies using autogenous bone in peri-implantitis therapy are rarely found, they do report favorable potential of vertical bone regeneration. Moreover, while membranes are an inherent part of the guided bone regeneration, a 5-year follow-up study demonstrated clinical and radiographic improvements with and without a membrane. The administration of systemic antibiotics is frequently performed in clinical studies observing regenerative surgical peri-implantitis therapy, but the analysis of the literature does not support a positive effect of this medication. Most studies for regenerative peri-implantitis surgery recommend the removal of the prosthetic rehabilitation and the use a marginal incision with a full-thickness access flap elevation. This allows for a good overview for regenerative procedures with a certain risk of wound dehiscences and incomplete regeneration. An alternative approach referring to the poncho technique may reduce the risk of dehiscence. The effectiveness of implant surface decontamination might have an impact on peri-implant bone regeneration without any clinical superiority of a certain technique. The available literature reveals that the success of peri-implantitis therapy is limited to the reduction of bleeding on probing, the improvement of the peri-implant probing depth and a small amount of vertical defect fill. On this basis, no specific recommendations for bone regeneration in surgical peri-implantitis therapy can be made. Innovative approaches for flap design, surface decontamination, bone defect grafting material, and soft tissue augmentation should be followed closely to find advanced techniques for favorable peri-implant bone augmentation.

Evidence has shown some improved clinical outcomes and morbidity reduction with the use of lasers for non-surgical periodontal therapy due to ablation, vaporization, hemostasis, and field sterilization. The purpose of this systematic review is to evaluate and compare studies involving lasers as monotherapy or adjunctive to surgical periodontal treatment. Electronic and manual searches were conducted by two independent reviewers in several databases for articles written in English up to December 2014. Articles were included in this review if they reported outcomes of surgical periodontal therapy with and without the use of lasers. The primary outcome was probing depth (PD), and secondary outcomes were measured changes in clinical factors such as clinical attachment level (CAL) and gingival recession (GR). For the comparative studies included, the pooled weighted mean difference (WMD) and 95% confidence interval (CI) of each variable were calculated using random-effects meta-analysis. Eight and nine articles were included in the quantitative and qualitative analyses, respectively. Although low-to-moderate risk of bias was detected, high heterogeneity among studies was found. In flap surgery with or without laser treatment, there was no statistically significant difference in primary outcome. Similarly, in guided tissue regeneration (GTR)/enamel matrix derivative (EMD) with and without laser treatment, the WMD of PD was negligible; however, the GTR/EMD group showed better outcomes (P = 0.005) than the laser group. Regarding the secondary outcomes, in the flap surgery group, the WMD of CAL gain was 1.34 mm, and the WMD of GR was -0.24 mm; no significant difference was detected between groups. In GTR/EMD with and without laser treatment, the WMD of CAL gain was 0.10 mm and the WMD of recession was -0.18 mm; again, no significant difference was detected between groups. The available evidence is insufficient to support the effectiveness of dental lasers as an adjunct to resective or regenerative surgical periodontal therapy. However, precautions must be exercised when interpreting the results of this study because of the small sample size and high heterogeneity among studies.

The healing potential of bone is sufficient to restore simple fractures, which are generally treated by standard conservative or surgical therapy. However, in some cases, reparative osteogenesis does not result in structural and functional recovery of the bone. Extended bone defects following trauma or cancer resection or non-unions of fractures may require more sophisticated treatment. In these cases, bone grafting procedures, segmental bone transport, distraction osteogenesis or biomaterials are applied for reconstruction.

The increasing life expectancy in many parts of the world has led to an epidemiologic transition in the leading causes of death from infectious diseases and acute illness to chronic illness related to organ or tissue degeneration. For example, chronic non-communicable diseases, including cardiovascular diseases, chronic respiratory diseases and cancer now account for an estimated 80% of total mortality and 70% of disability-adjusted life-years lost in China (1). Despite the recent advances in medical and surgical therapies, a large number of patients with cardiovascular diseases remain severely symptomatic with poor clinical outcomes. Many currently untreatable cardiovascular disorders arise from disease process due to significantly loss of cardiomyocytes that do not otherwise regenerate. As a result, stem cell therapy has been explored as potential treatment to limit the progression of diseases or to regenerate damaged heart in patients with different cardiovascular diseases. Indeed, stem cell therapy was conceptualised more than a decade ago in the treatment of acute myocardial infarction (2). The articles in this Theme issue of Thrombosis and Haemostasis tackle several of the important topics in cardiovascular regeneration using stem cell therapy. Based on the initial encouraging results in the experimental studies, numerous clinical studies in recent years have been shown that cell-based therapy can improve symptoms and cardiac function, and limit infarct size and adverse ventricular remodelling in patients with acute myocardial infarction, chronic myocardial ischaemia and congestive heart failure. Siu et al. (3) present a critical overview on the current status, including those data from the randomised clinical trials on the use stem cell therapy for myocardial regeneration. Despite the promising initial clinical results, the beneficial effects are at best modest, and several major issues, such as the optimal timing, cell types and mode of delivery need to be addressed in the ongoing clinical trials. Furthermore, additional strategies to improve cell survival and engraftment should also be developed to overcome the potential hurdles related to cell-based therapy. One of the major limitations of clinical success of stem cell therapy is the low cell retention and engraftment after transplantation. Accurate methods for cell tracking as well as quantification of cell survival are needed to determine the optimal method to enhance cell retention and engraftment. In addition to conventional laboratory techniques, novel in vivo imaging methods have been developed and can provide serial noninvasive assessment of cell fate. Ransohoff and Wu (4) describe the basic principles and techniques of radionuclide imaging, magnetic resonance imaging, bioluminescence imaging, and fluorescence imaging for assessing cell engraftment, discuss their strength and critically discuss their limitations. The development of these techniques to track cell fate and viability not only can provide important insight into the stem cell biology after transplantation, but also help to evaluate new techniques, such as genetic modification, bioengineering and cell preconditioning to optimise cell engraftment (3). The other important obstacle for cardiac regeneration with stem cell therapy is the Correspondence to: Hung-Fat Tse, MD, PhD Cardiology Division, Department of Medicine The University of Hong Kong, Queen Mary Hospital Hong Kong, China Tel.: +852 2855 3598, Fax: +852 2818 6304 E-mail: hftse@hkucc.hku.hk

The present study aimed at investigating the impact of defect configuration on the clinical outcome of surgical regenerative therapy of peri-implantitis lesions using a natural bone mineral in combination with a collagen membrane (NBM+CM). Twenty-seven patients (n=27 defects) exhibited three different types of peri-implantitis lesions including either Class Ib (buccal dehiscence+semicircumferential), Class Ic (buccal dehiscence+circumferential), or Class Ie (circumferential) intra-bony defects (n=9 defects per group). All defects were treated with access flap surgery and the application of NBM+CM. At 6 and 12 months, Class Ie defects tended to reveal higher changes in the mean probing depth (PD) and clinical attachment level (CAL) values when compared with Class Ib and Class Ic groups. However, significant differences were only observed at 6 months (PD: 2.9 +/- 0.3 versus 1.4 +/- 0.5 versus 1.3 +/- 0.7 mm; CAL: 2.5 +/- 0.5 versus 0.9 +/- 0.8 versus 0.9 +/- 0.7 mm). Site-level analysis has pointed to lowest PD and CAL changes at the midbuccal aspect of Class Ib and Class Ic groups. Defect configuration may have an impact on the clinical outcome following surgical regenerative therapy of peri-implantitis lesions. While Class Ie defects seem to be promising in conjunction with NBM+CM, Class Ib and Class Ic may be considered as unfavourable.

Clinical studies have evaluated the effect of conventional periodontal surgical therapy. In general, although some clinical gain in tissue support may be attained, these therapies do not support regeneration of the periodontal attachment. Even though the biological possibility of periodontal regeneration has been demonstrated, the clinical application of this intrinsic potential appears difficult to harness; thus also conceptually most intriguing candidate protocols face clinical challenges. In this review, we explore the bioclinical principles, condiciones sine quibus non, that unleash the innate potential of the periodontium to achieve clinically meaningful periodontal regeneration (i.e. space-provision, wound stability and conditions for primary intention healing). Moreover, limiting factors and detrimental practices that may compromise clinical and biological outcomes are reviewed, as is tissue management in clinical settings.

The management of periodontal defects has been an ongoing challenge in clinical periodontics. In the recent past, attention has been focused more on regenerative and reconstructive therapies i.e. bone grafts, guided tissue regeneration, root conditioning, polypeptide growth factors, rather than on respective therapies. These therapeutic measures are shown to be limited in the predictability of healing and regenerative response in the modem clinical practice because oral environment presents several complicating factors that border regeneration. The 21st century appears to represent a time in history when there is a convergence between clinical dentistry and medicine, human genetics, developmental and molecular biology, biotechnology, bioengineering, and bioinformatics, resulting in the emergence of novel regenerative therapeutic approaches and focusing mainly on non surgical modalities. The purpose of this article is to provide a review of the various non surgical therapies in use today. Future direction in this ever-changing field is also discussed. Techniques currently in use are reviewed and evaluated. They include Probiotics, Ozone therapy, Photodynamic therapy, Gene therapy, RNA interference, Nanotechnology, Perioprotect, TIPS &amp; BOST. DOI: http://dx.doi.org/10.3329/bjdre.v4i2.20254 Bangladesh Journal of Dental Research and Education Vol.4(2) 2014: 78-82